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Building Osteogenic Microenvironments With Strontium-Substituted Calcium Phosphate Ceramics

Ben Wan 1Renxian Wang 1Yuyang Sun 1Jingjing Cao 1Honggang Wang 1Jianxun Guo 1Dafu Chen 1

Front Bioeng Biotechnol doi: 10.3389/fbioe.2020.591467. eCollection 2020.


Bioceramics have experienced great development over the past 50 years. Modern bioceramics are designed to integrate bioactive ions within ceramic granules to trigger living tissue regeneration. Preclinical and clinical studies have shown that strontium is a safe and effective divalent metal ion for preventing osteoporosis, which has led to its incorporation in calcium phosphate-based ceramics. The local release of strontium ions during degradation results in moderate concentrations that trigger osteogenesis with few systemic side effects. Moreover, strontium has been proven to generate a favorable immune environment and promote early angiogenesis at the implantation site. Herein, the important aspects of strontium-enriched calcium phosphate bioceramics (Sr-CaPs), and how Sr-CaPs affect the osteogenic microenvironment, are described.


In summary, integrating Sr ions into CaPs offers an alternative to biologics in the design of bioactive materials. It is of low cost, has a longer shelf life, and presents low systemic risk compared to growth factors. These added benefits make Sr as therapeutic agent attractive in tissue engineering and regenerative medicine applications (Jiménez et al., 2019Prabha et al., 2019Mao et al., 2020). However, the mechanism of osteoinduction of SrCaPs remains complicated because inflammation and angiogenesis accompany the entire process of bone healing. In light of the previous studies, we propose a hypothesis for the osteoinduction mechanism of SrCaPs: SrCaPs build the osteoinductive microenvironment of the host bone-implant interface (. Functional ion release and apatite layer formation on the surfaces of SrCaP ceramics allow them to interact with cells and extracellular matrices in the host system, providing bioactive bonding to bone. Specifically, a higher local concentration of Sr stimulates the osteoblastic differentiation of MSCs , induces macrophage polarization toward a pro-regenerative M2 phenotype , and contributes to angiogenesis . Collectively, understanding the biological microenvironment of implant-to-tissue interactions at the bone site is important for the development of high-performance bioceramics.